NMR is usually pursued in a setup based on a highly homogenous static magnetic field with spatial variation of less than 1 ppm, creating nuclear spin precession at a corresponding narrow frequency band of frequencies. However, this setup suffers from the need to employ strong and homogenous magnets, radio frequency (RF) and gradient coils that usually surround the examined sample, such as blood sample or tissue biopsy, and are a major factor in the relative complexity and the high cost of such systems.
NMR has found applications in magnetic nuclear resonance imaging (MRI) (as its sensitivity to the chemical characteristics of tissue components makes it the modality of choice for tissue characterization and differentiating soft tissues), fluid chemical analysis of small molecules and biomolecules (protein-ligand interactions, protein folding, protein structure validation, protein structure determination), solid state analysis (structural), dynamics of time-variable systems (functional MRI), etc.
A company called “TopSpin Medical” has recently revealed an intra venous magnetic nuclear resonance imaging (IVMRI) catheter with a static magnetic field of about 0.2 Tesla generated by strong permanent magnets located at the tip of a catheter. This company has developed a self contained “inside-out” miniature MRI probe in a tip of an intravascular catheter that allows for local high-resolution imaging of blood vessels without the need for external magnets or coils. This probe is shown in FIG. 1. The advantages of this technique range from the very practical aspect of a low-cost system, since no expensive external setup is required, accessibility to the patient during the procedure, compatibility with existing interventional tools and finally resolution and diffusion contrast capabilities that are unattainable by conventional clinical MRI, due to the strong local gradients created by the probe and its proximity to the examined tissue. This intravascular probe serves as a first example for a wide range of applications for this method, which in the near future may revolutionize the field of clinical MRI. The medical applications for this technology include for instance detection and staging of prostate cancer, imaging tumors in the colon, lung and breast and intravascular imaging of the peripheral vasculature.
Micro NMR coils are also known for a skilled man in the art. Developments of these “micro MRI” devices depend on the existence of high quality receiving coils. Microelectromechanical systems (MEMS) breakthroughs have made possible this new technology for the micro fabrication of Helmholtz micro coils for NMR spectroscopy. These Helmholtz micro coils demonstrate superior NMR performance in terms of spin excitation uniformity compared to planar micro coils. The improved spin excitation uniformity opens the way to advanced chemical analysis by using complex RF-pulse sequences. The fabricated Helmholtz coils have Q-factor greater than 20 due to electroplated coil turns and vias, which connect the lower and upper turns. For analyzing living cells, mechanical filters can be integrated for sample concentration and enhanced detection.
NMR requires orienting a part of the nuclei magneton (spins) population along a chosen spatial direction. When oriented, the population is in a polarized state. This is usually achieved with strong magnetic fields, which are not attenuated by diamagnetic materials (biological tissue, fluids etc.). The net polarization achieved using magnetic fields is usually on the order of 5 to 25 parts per million. The nuclei spins of a material can be locally oriented by radiating the sample with circularly polarized light. Methods using circularly polarized light are able to achieve high levels of polarization, up to 40%, under the right circumstances. Polarizations in this order of magnitude are considered hyperpolarized. Hyperpolarizability is obtained through the hyperfine spin-spin interaction electron-nucleus, the electron-photon spin exchange and the electronic-spin population saturation due to Fermi's exclusion principle applied to molecule's electrons.
Optical pumping is used to produce hyperpolarized gases. Hyperpolarized gases have found a steadily increasing range of applications in MRI and NMR. They can be considered as a new class of MR contrast agent or as a way of greatly enhancing the temporal resolution of the measurement of processes relevant to areas as diverse as materials science and biomedicine. The physics of producing hyperpolarization involves irradiating samples of Na with intense circularly polarized lasers of a wave length corresponding to one of the absorption bands for Na, followed by a “mechanical” polarization transfer to inert 129Xe. The last is used as contrast agents in MRI and polarization transfer for other nuclear species for low-field imaging.
The NMR effect can be observed and measured with optical methods. All Optical NMR hyperfine interactions allow for flip-flop spin scattering. This means that an electron can flip its spin by flipping simultaneously a nucleus into the other direction. This leads to a dynamic polarization of the nuclear spins. If the electron spin levels are saturated by a driving field, i.e. the population of the upper spin state is made equal to that of the lower state, such flip-flop processes try to re-establish thermal equilibrium, resulting in a nuclear spin polarization, which is described by a Boltzmann factor where the electron Zeeman splitting enters. Because the electron splitting is usually 1000 times larger than the nuclear splitting, the nuclei end up in an up to 1000 times enhanced polarization compared to their thermal equilibrium value—also known as an Overhauser effect.
Yet another application of light angular momentum with magnetons is a high sensitivity-high frequency magnetometer. This solves one of the challenges raised by observing NMR effects, which is being able to measure the transient response of the magnetic fields produced by spinning nuclei. A magnetometer has been demonstrated operating by detecting optical rotation due to the precession of an aligned ground state in the presence of a small oscillating magnetic field. The projected sensitivity is around 20 pG/pHz (RMS).
In 1992 Allen et al., “Optical angular momentum”, ISBN 0 7503 0901 6, verified the existence of light endowed with orbital angular momentum (OAM). Theoretical understanding and experimental evidence lead to applications, where light with OAM interacts with matter: optical tweezers, high throughput optical communication channels, optical encryption technique, optical cooling (Bose-Einstein condensates), entanglement of photons with OAM, entanglement of molecule quantum numbers with interacting photons OAM.
The Micro NMR is an appealing chemical analysis device for being included in an ePill device or in an inexpensive non-invasive blood analysis apparatus. It shall consume low power, be confined within a small volume and shall not include any paramagnetic materials (FDA). “TopSpin Medical” micro NMR or other “fixed magnet based” NMR are not suitable for the purpose, since these include a permanent magnet, require long acquisition time and hence consume power. An ePill is a small electronic device that is swallowed by a patient for performing an analysis of internal organs of the patient.
Photon-electron spin interaction has been extensively observed and modeled and it is the basis of the optical pumping technology for hyperpolarizability of gases. Unfortunately, this technique is not capable for producing fluid hyperpolarizability, due to thermal molecular movement and interactions.
Photon OAM interactions with nuclei has been recently analyzed as a method of controlling the spin-spin interaction within nuclei. It uses energetic X rays, not desirable for “in-vivo” applications.
Furthermore, by applying a constant magnetic field to a sample containing N nuclei, at room temperature, one can calculate the maximum number of oriented nuclei (Boltzmann distribution), which is around 10−5N. In order to extract a significant magnetic signal from the sample, one has to implement high quality factor coils or enlarge the size of the sample. In both cases the volume occupied by the receiver shall increase, which makes the permanent magnet micro NMR difficult to integrate within an ePill.
Thus, the object of the present invention is to provide an improved method and apparatus for a sample analysis based on NMR spectroscopy.